Abstract 437: Treatment with Recombinant Placental Growth Factor Enhances both Angiogenesis and Arteriogenesis and Improves Survival after Myocardial Infarction.
Background: Recent studies indicated that therapeutic angiogenesis with vascular endothelial cell growth factor-A (VEGF-A) is not always effective in acute myocardial infarction (MI), mainly because it induces only immature vasculature. Placental growth factor (PlGF), a member of VEGF family, is different from VEGF-A in receptor specificity. PlGF specifically binds to VEGF receptor-1 (flt-1), though VEGF-A binds to both VEGF receptors 1 and 2. Recent our clinical work demonstrated that PlGF is rapidly produced within infarct myocardial tissue, and the plasma level of PlGF is positively correlated with number of monocytes and CD34 positive cells, and improvement of left ventricular function. However, therapeutic effects of PlGF on MI are not understood.
Methods and Results: One day before ligation of coronary artery, recombinant human PlGF (rhPlGF) (10μg) was infused into the peritoneal cavity of C57BL/6 mice through subcutaneously implanted osmotic mini pump until 2 days after the ligation. After 28 days, survival rate was significantly higher in rhPlGF-treated Group (70.0%) than PBS-Group (33.3%) (p<0.05). Seven days after MI, the infarct area, stained by 1.5% TTC (2,3,5-triphenyltetrazolium chloride), was smaller in rhPlGF-treated group (4.25±2.04mm2) than PBS-group (5.95±1.54mm2) (p<0.05), and it indicates exogenous PlGF suppressed cardiac remodeling. Echocardiography also revealed that left ventricular diastolic diameter was decreased (rhPlGF: 4.50±0.46mm, PBS: 5.14±0.38mm p<0.01), and ejection fraction was increased in rhPlGF-treated group (rhPlGF: 40.6+9.17%, PBS: 25.7±7.23% p<0.01). Histological analysis showed that both CD31-positive vascular endothelial cells (rhPlGF: 644.6+90.54/mm2, PBS: 459.0+73.89/mm2 p<0.01) and a-smooth muscle actin-positive vessels (rhPlGF: 31.6+7.20/mm2, PBS: 23.5+7.41/mm2 p<0.01) was increased at infarct area, and it implied that both angiogenesis and arteriogenesis contributes to the improvement of cardiac function.
Conclusion: rhPlGF-treatment preserved left ventricular function and inhibited post-infarct remodeling by enhancing neovascularization and arteriogenesis, through which rhPlGF-treatment improved survival rate after myocardial infarction.